Оценка фармацевтической эквивалентности таблетированных форм препаратов «Метадоксил» и «Алкодез ІС» с использованием теста «Растворение»

На сегодняшний день очевидна актуальность проблемы рационального использования теста «Растворение» при изучении фармацевтической эквивалентности лекарственных средств на разных этапах их регистрации и перерегистрации. В статье изложена методика проведения теста «Растворение» с целью оценки фармацевтической эквивалентности таблетированных форм воспроизведенного препарата «АЛКОДЕЗ® ІС» (ОДО «ИНТЕРХИМ», Украина) и референтного препарата «Метадоксил» (“Laboratori Baldacci S.p.A”, Италия). Результаты проведенного исследования демонстрируют подобие профилей растворения изучаемого генерического и референтного препаратов, что доказывает их фармацевтическую эквивалентность.Today relevance of the problem of rational use of test “Dissolution” in the study of pharmaceutical equivalence of drugs in different stages of registration and re-registration is obvious. The purpose of this work is to develop the methodology of the test “Dissolution” to assess the pharmaceutical equivalence of the generic drug “ALKODES® ІC” 0.5 g tablets (SLC “INTERHIM”, Ukraine), and the reference product “Metadoxil” 0.5 g tablets (“Laboratori Baldacci S.p.A”, Italy). The test was performed on 12 tablets of each series of drugs. For determining the dissolution of tablets the paddle apparatus was used. As dissolution media it was used 0.1 M hydrochloric acid; acetate buffer pH 4.5; 0.05 M phosphate buffer pH 6.8. The samples were collected at 5, 10, 15, 25, 35, 45, 60 min after starting the test. Amount of metadoxine (active ingredient) was released from the tablet in standard media and was determined spectrophotometrically by method of standart. The equivalence of dissolution profiles were evaluated by calculating the similarity factor (f2). Values of coefficient of similarity (50<f2<100) demonstrate the similarity of dissolution profiles studied generic and reference products, which proves their pharmaceutical equivalence

CARDIOPROTECTIVE AND NEPHROPROTECTIVE EFFECTS OF ANGIOTENSIN CONVERTING ENZYME INHIBITOR RAMIPRIL

There is grate interest to ACE inhibitors which have cardioprotective and neproprotective effects. Ramipril efficacy in ischemic heart disease prevention as well as ramipril positive effect on myocardium in adolescents is presented on the base of some trails. Ramipril ability to delay of diabetic and non-diabetic nephropathy progression is also discussed

INTERRELATION BETWEEN PERSISTENT NECROSIS OF CARDIOMYOCYTES AND PROGNOSIS IN PATIENTS WITH CHRONIC HEART FAILURE

Background. Chronic heart failure (CHF) progression is accompanied by remodeling of muscular, collagen and vascular elements of myocardium. This can lead to increase in serum concentrations of myocardial lesion markers (cardiac troponin I (TrI) and myoglobin) which seem to correlate with poor prognosis in patients with CHF.Aim. To estimate correlations between cardiac TrI, myoglobin, creatine phosphokinase MB-fraction (MB-CPK) serum concentrations and disease severity and prognosis in CHF patients.Material and methods. Fifty eight patients with CHF of different etiology were included into the study. Physical examination, clinical and biochemical blood assays, chest X-ray study, echocardiography and ECG daily monitoring (initially and at the end of the study) were carried out. TrI and myoglobin levels were estimated by immunoenzymometric assay. The follow-up period was 6 months. The following end points were used: CHF worsening caused hospital admission, acute myocardial infarction, and lethal outcome.Results. Mean TrI and myoglobin concentrations equaled 0.04 [0.02; 0.06] ng/ml and 62.95 [35.86; 77.28] μg/l, respectively. Demographic characteristics of patients (gender, age) did not influence these markers levels. TrI concentration correlated with CHF severity: it was significantly higher in patients with CHF of functional class (FC) III-IV than in those with CHF of FC I-II (p&lt;0.001). Negative correlation was revealed between TrI level and ejection fraction (p&lt;0.001). TrI concentration was significantly higher in patients with life-threatening ventricular arrhythmia than in patients without it (p=0.001). Besides, TrI level was significantly higher in patients with registered end points than in those with stable CHF course (p=0.001).Conclusion. TrI correlates with CHF severity and probably has prognostic value in these patients

Structural mechanisms of the degenerate sequence recognition by Bse634I restriction endonuclease

Restriction endonuclease Bse634I recognizes and cleaves the degenerate DNA sequence 5'-R/CCGGY-3' (R stands for A or G; Y for T or C, '/' indicates a cleavage position). Here, we report the crystal structures of the Bse634I R226A mutant complexed with cognate oligoduplexes containing ACCGGT and GCCGGC sites, respectively. In the crystal, all potential H-bond donor and acceptor atoms on the base edges of the conserved CCGG core are engaged in the interactions with Bse634I amino acid residues located on the α6 helix. In contrast, direct contacts between the protein and outer base pairs are limited to van der Waals contact between the purine nucleobase and Pro203 residue in the major groove and a single H-bond between the O2 atom of the outer pyrimidine and the side chain of the Asn73 residue in the minor groove. Structural data coupled with biochemical experiments suggest that both van der Waals interactions and indirect readout contribute to the discrimination of the degenerate base pair by Bse634I. Structure comparison between related enzymes Bse634I (R/CCGGY), NgoMIV (G/CCGGC) and SgrAI (CR/CCGGYG) reveals how different specificities are achieved within a conserved structural core

Diagnosis and treatment of the irritable bowel syndrome: clinical guidelines of the Russian gastroenterological association and Russian association of coloproctology

Aim of publication. To present recent RGA evidencebased medicine centered guidelines on diagnosis, rational pharmacotherapy and management of irritable bowel syndrome (IBS). Summary. IBS - is a functional bowel disorder is manifested by recurrent abdominal pain that develops at least once per week and characterized by at least two of the following signs: it is related to bowel movements, associated to the change in stool frequency and/ or shape. These symptoms should be present in the patient for the last 3 months at overall duration of observation for six months or more. Similar to other functional gastrointestinal disorders, the diagnosis of IBS can be established at compliance of symptoms to Rome IV criteria and the absence of organic gastrointestinal diseases that could cause patient’s symptoms. Due to complexity of differential diagnostics, IBS should be considered as diagnosis by exclusion that require following investigations: clinical and biochemical blood tests; IgA or IgG anti-tissue transglutaminase antibodies; thyroid hormone levels; fecal occult blood test; glucose or lactulose hydrogen breath test for bacterial overgrowth syndrome; stool test for coliform bacteria, stool test for Clostridium difficile toxins A and B; fecal calprotectin level; abdominal ultrasound; upper and lower endoscopies, at indications - with biopsies. IBS treatment requires diet and lifestyle modifications, intake of pharmacological agents and psychotherapy. Antispasmodic medications (e.g.: hyoscine butylbromide, pinaverium bromide, mebeverine) are recommended for abdominal pain relief. For diarrhea-predominant IBS such medications as loperamide hydrochloride, dioctaedric smectite, non-absorbable antibiotic rifaximin and probiotics may be prescribed. For treatment of IBS with constipation use of bulking agents (psyllium), osmotic laxatives (macrogol 4000, lactulose), laxatives stimulating intestinal motility (bisacodyl) may be applied. Enterokinetic agent prucalopride may be prescribed at inefficacy of laxatives. Peripheral opioid agonists (trimebutine maleate) normalizing intestinal motor activity via action on different subtypes of peripheral opioid receptors, combined plant-derived medication STW 5 are applied as well. Conclusion. Implementation of clinical guidelines can determine timely diagnosis and treatment of various IBS types. The IBS is characterized by scalloping course with relapse periods that are provoked by psychoemotional stress and remissions. The risk of organic bowel diseases IBS patients is not higher, than in total population

Social and demographic characteristics, features of disease course and treatment options of inflammatory bowel disease in Russia: results of two multicenter studies

Background: Epidemiological studies  performed in different countries  have identified a number  of trends  that  allow to predict  the problems  related to the  prevalence  of inflammatory  bowel  diseases  (IBD),  their  severity  and  healthcare resources utilization. Aim:  To  present   comparative   results of two large epidemiological  studies of IBD in the Russian Federation (RF), i.e. ESCApe and ESCApe-2. Materials     and     methods:     Two    multicenter cross-sectional cohort studies with a similar design were performed  at three-year interval. The studies had the common aim: to identify social and demographic and clinical particulars of ulcerative colitis (UC) and Crohn’s disease (CD) in RF, as well as treatment options. Twenty (20) centers of gastroenterology from 17 RF regions participated in the ESCApe (2010–2011) and 8 centers from 7 RF regions in the ESCApe-2 study (2013–2014). Results: The ESCApe study included 1797 patients (1254 UC and 543 CD), whereas   the   ESCApe-2  included   1000  patients (667 UC and 333 CD). Patient demographic and social characteristics: In both  studies, female: male ratio was similar in UC and CD. Patients’ age was almost identical: in UC, median  age was 38 years and 40 years in ESCApe and ESCApe-2, respectively; in CD the  corresponding  values were  36 and 35 years. In ESCApe, the peak UC onset was at the age of 21 to 40 years, whereas in CD it was shifted towards younger age (22.5% of the patients  manifested before 20 years) and the peak incidence was in three age groups (below 20 years, 21 to 30 and 31 to 40 years).  A statistically significant difference between CD and  UC was found  only in the  age group  of 11 to 20 years (22.5% vs. 13.6%, respectively, p &lt; 0.01). In ESCApe-2, median age of disease onset in UC and CD was approximately 30 years. In both  studies, urban:rural ratio for UC and CD was 4:1. In ESCApe, the proportion of current  smokers among  CD patients  was almost  two-fold  higher than  among  those  with  UC (15.6  and  8.8%,  respectively, p &lt; 0.001); the same trend was found in ESCApe-2 (15 and 7.3%, p &lt; 0.001). Socioeconomic characteristics of patients in both studies were similar: 50 to 60% were at work (professional occupation and income levels were not studied); in ESCApe 30.9% of UC patients and 40.9% of CD patients had legal disability due  to various reasons  (including that related to UC and CD in 12,6 and 14.9%, respectively), whereas in ESCApe-2 the respective proportions  were  35.7 and  51.1%.  Clinical characteristics of patients: The time from the  first UC symptoms to diagnosis  was similar in both  studies  (median, 5 months  in ESCApe and 4 months  in ESCApe-2); in CD patients  these parameters were significantly different in both studies (12 vs. 1 month). As for the severity of the disease, the UC patients  in ESCApe had  mild disease  in 16%, moderate in 53%, and severe in 31%, whereas the respective proportions among  the  CD patients  were 21, 44, and  35%. In ESCApe-2, there were no patients  with severe disease;  mild and  moderate UC were  diagnosed  in 51.3 and  46.6% of the  patients, respectively, and mild and moderate CD, in 52.3 and 47.3%. The frequency of left-side UC was similar: 38% in ESCApе and 34% in ESCApе-2. Proctitis was more frequent in the  first study  (33 vs. 11%, p &lt; 0.01), and  total UC was more frequent  in the second  study (29 vs. 55%, p &lt; 0.02). There were no significant differences between ESCApe and ESCApe-2 in the main CD localizations: terminal ileitis was seen  in 31.3 and 35.4% of the  patients,  respectively,  ileocolitis in 33.4 and 37.8%, colitis in 25.6 and 32.1%. The upper gastrointestinal involvement In ESCApе was found 4.4%, and mixed involvement  in 5.3%. In both studies, extra-intestinal  manifestations were more frequent  in CD, than  in UC: in ESCApe, 33.1% and 23% (р &lt; 0.05), and in ESCApe-2 in 41.7 and 29.4%, respectively   (р &lt; 0.05).   Peripheral   arthropathies were  most  frequent. Ankylosing spondylitis  was found in CD only, and primary sclerosing cholangitis, only in UC. Aphthous  stomatitis  was significantly more prevalent in CD in both studies. There were no significant differences in all other extra-intestinal symptoms  (eye and skin involvement). Treatment characteristics: Treatment options before the  study entry, as well as at the  study inclusion visit were analyzed. In ESCApe, the majority of the patients  had not been given any treatment before the study entry (49.1% with UC and 40.5% with CD). Three years later  the  situation  was changing: in ESCApe-2, the  proportion of treatment-naïve patients was 2.5 to 3-fold lower (15.3% with UC and 14.4% with CD), which was most probably related to increasing  awareness  of physicians. Before the study entry, most  patients  (40 to 70%) had  been treated with 5-aminosalicylic acid (5-ASA). Before the  second  study,  the  patients   were  more  frequently  treated with  glucocorticosteroids (GCS), immunosuppressors and  genetically  engineered biological agents  (GEBA),  but  with no significant differences  from the  first study. 5-ASA prevailed also  among  the  agents  that  were  administered during  the  inclusion visits in both  studies  (80 to 90% UC patients  and  about  70% of CD patients). Compared   to  ESCApe,  in  ESCApe-2  there   was a trend  towards  lower rate of GCS administration in UC and CD, but the differences did not reach the significance level. It may be explained  by the absence of severe IBD types in ESCApe-2. In ESCApe, immunosuppressors were rarely used (in 14.4% of the UC patients  and in 26.8% of the CD patients); however, in ESCApe-2 there were administered more  frequently: up to 35.9% of the  UC patients and 55.1% of the CD patients  (р &lt; 0.01 for both cases). It was unknown  if immunosuppressors were used as monotherapy or in combination with GCS. Three years later, the rate of GEBA administration was also higher, but  this increase  was significant only in CD: 28.3%  in ESCApe-2 vs. 9.2% in ESCApe (р &lt; 0.01). According to the results of ESCApe, in the UC patients steroid resistance was seen in 23% and steroid dependency in 21%, whereas in the CD patients these values were 24 and 27%, respectively. In ESCApe-2 these  parameters were not assessed. Conclusion:  Both studies  showed  a  number   of patterns coinciding  with  the  world  trends,  such as age and gender  distribution  of UC and CD patients, age at manifestation, the proportion of urban to rural residents, smoking status, prevalence and types of extra-intestinal  symptoms. Unlike in European countries, moderate and severe forms of UC with extensive involvement are prevalent in RF. Low prevalence  of mild and limited types of IBD is to be explained by underdiagnosis. Of note is the high proportion of patients  with UC and CD treated with 5-ASA, although in CD these  agents  have demonstrated low efficacy. The rates of immunosuppressors  and GEBA administration significantly increased  in the second  study, most likely, due to the  implementation of a  system  of educational measures. Nevertheless, the rate of GEBA use in IBD remains low, which is to be related to their insufficient availability. In total, steroid resistance / steroid dependency rate amount  to almost half of UC and CD cases. In general, some positive changes  in the patient  management are  obvious  in the  second study. However, monitoring  these  changes  over time could only be possible if similar studies would be performed at regular intervals